Catalytic Dicyanative 5‐exo‐ and 6‐endo‐Cyclization Triggered by Cyanopalladation of Alkynes

A stereoselective dicyanative 5‐exo‐ and 6‐endo‐cyclization using various enynes has been investigated. The mode of cyclization is critically controlled by the structure of the substrates. For example, N‐allyl derivatives prefer 5‐exo‐cyclization, while methacryloyl amides are transformed to the corresponding lactams with tetra‐substituted carbons at the alpha‐position via 6‐endo‐cyclization. Both reactions include syn‐cyanopalladation to carboncarbon triple bonds in the initial step, and sequential cyclization followed by reductive elimination in one operation enables the construction of the highly functionalized nitrogen heterocycles. The scope of suitable substrates and a proposed mechanism are also described.     

Studies of reaction mechanisms during stabilization of electrospun polyacrylonitrile carbon nanofibers

Various reaction mechanisms such as cyclization, oxidation, dehydrogenation, and crosslinking are studied during stabilization of electrospun polyacrylonitrile nanofibers using different in situ techniques such as differential scanning calorimetry (DSC), shrinkage measurement, and dynamic mechanical analysis (DMA). DSC results show that oxidation preferentially occurs in cyclized structure. It is also found that the cyclization reaction has the highest activation energy followed by oxidation/dehydrogenation and crosslinking reactions. In situ shrinkage measurement and DMA data are used to study the extent of cyclization and cross‐linking reactions, respectively, in air. Comparing the in situ shrinkage measurement with DSC data, it is found that cyclization reaction in air progresses in two different mechanisms such as radical cyclization, which depends only on the temperature and ionic cyclization, which is limited by the rate of oxygen diffusion. It is found that complete cyclization time occurs at about 189 min for isothermal heat treatment at 260°C with 5°C/min ramp, while cross‐linking reaction becomes dominant at 132 min. POLYM. ENG. SCI., 58:1315–1321, 2018. © 2017 Society of Plastics Engineers     

Comprehensive and quantitative study on the thermal oxidative stabilization reactions in poly(acrylonitrile‐co‐itaconic acid) copolymer

Thermal oxidative stabilization (TOS) reactions, mainly cyclization, oxygen uptake, dehydrogenation, crosslinking, and disproportionation termination of cyclization in poly(acrylonitrile‐co‐itaconic acid) (PAI), are tracked quantitatively by the combination of second‐derivative and cure‐fitting operations in the Fourier transform infrared spectroscopy spectra (FTIR) range of 1800–1000 cm^?1 and 2300–2100 cm^?1. Except the cyclization and disproportionation of cyclization are chemical‐reaction‐controlled process, the other three reactions are both diffusion‐controlled and chemical‐reaction‐controlled processes. The formation of free and conjugated carbonyl group need the optimal cyclization rate, adequate unreacted linear PAI chains, and appropriate oxidation ability coordinated. The higher temperature, the faster rate and the higher extent of the cyclization and the crosslinking reactions as well as the faster disproportionation termination of cyclization. The length of the formed cyclic structures became shorter as the evolution of TOS process, especially for 265 °C. The crosslinking, oxygen uptake, dehydrogenation, and termination of cyclization reactions become dominant with the proceeding of TOS process, especially as the cyclization extent above 0.8 and at high temperature such as 265 °C. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45934.     

4-Piperidones from Enantiomerically Pure Enones. Synthesis of 6-alkylsubstituted 4-oxo-pipecolic acid derivatives

The cyclization of the enantiomerically pure α,β-unsaturated ketone 1 , an aliphatic aldehyde 3 and ammonia or benzylamine gives diastereoselectively cis-piperidones 4/4 ′. Although only modest yields were obtained, the presented cyclization has the advantage of being a single step reaction. The products 4 can serve as precursors for all-cis-4-hydroxy-piperidones 5 and novel pipecolic acid derivates 9 .     

Mechanistic Studies on Trichoacorenol Synthase from Amycolatopsis benzoatilytica

Isotopic labeling experiments performed with a newly identified bacterial trichoacorenol synthase established a 1,5-hydride shift occurring in the cyclization mechanism. During EI-MS analysis, major fragments of the sesquiterpenoid were shown to arise via cryptic hydrogen movements. Therefore, the interpretation of earlier results regarding the cyclization mechanism obtained by feeding experiments in Trichoderma is revised.     

Regioselective synthesis of indole-annulated sulfur heterocycles by tri-n-butyltin hydride-mediated aryl radical cyclization

2-[(2-Bromobenzyl)sulfonyl]indoles under Bu₃SnH-mediated aryl radical cyclization furnished exclusively the benzo[c]thiopyrano[2,3-b]indoles in 56–61% yields via 6-endo-trig cyclization whereas 2-[(2-bromobenzyl)sulfanyl]indole 3a gave only the β-scission product.     

Properties of the Amide Bond Involving Proline 4,5-methanologues: an Experimental and Theoretical Study

Herein we disclose a combined experimental and theoretical study on the conformational properties of amide bonds involving diastereomeric 4,5-methano-L-proline congeners as N-acetyl ethyl esters and dimeric amide ethyl esters as substrates for cyclization to diketopiperazines. The results are discussed in light of density functional theory calculations aimed at delineating the importance of the n→π* stabilization of the trans-amide conformations. The transitions states for the cyclization of diastereomeric 4,5-methano-L-proline ethyl esters to diketopiperazines were calculated and correlated to the experimental studies.     

Attempted Synthesis of Bowl-Shaped Polycyclic Aromatic Hydrocarbons via Oxidative Electrocyclization. Products from the Dications of Dibenzo [g,p] chrysene,Tetrabenzo[5.5]fulvalene,and Diphenylmethylidenefluorene

Synthesis of diindeno[1,2,3,4-defg: 1′,2′,3′,4′-mnop]chrysene (1), a portion of the C₆₀ surface, was attempted through oxidative cyclization of tetrabenzo[5.5]fulvalene (2), dibenzo[gp]chrysene (3), and diphenylmethylidenefluorene (4) by SbF₅/SO₂CIF. Compounds 2 and 3 were oxidized to dications which then underwent a single cyclization to give precursors to 1. Compound 4 underwent two oxidative cyclizations to give a precursor to 1. AM1 calculations of the possible products from cyclization were consistent with preferential formation of the cyclized product with the lower ΔHf. Oxidative cyclization may offer a one-pot synthetic alternative for the preparation of unusual polycyclic aromatic hydrocarbons.     

Cyclization of the Antimicrobial Peptide Gomesin with Native Chemical Ligation: Influences on Stability and Bioactivity

Gomesin is an 18‐residue peptide originally isolated from the hemocytes of the Brazilian spider Acanthoscurria gomesiana. A broad spectrum of bioactivities have been attributed to gomesin, including in vivo and in vitro cytotoxicity against tumour cells, antimicrobial, antifungal, anti‐Leishmania and antimalarial effects. Given the potential therapeutic applications of gomesin, it was of interest to determine if an engineered version with a cyclic backbone has improved stability and bioactivity. Cyclization has been shown to confer enhanced stability and activity to a range of bioactive peptides and, in the case of a cone snail venom peptide, confer oral activity in a pain model. The current study demonstrates that cyclization improves the in vitro stability of gomesin over a 24 hour time period and enhances cytotoxicity against a cancer cell line without being toxic to a noncancerous cell line. In addition, antimalarial activity is enhanced upon cyclization. These findings provide additional insight into the influences of backbone cyclization on the therapeutic potential of peptides.     

A Novel Rhodium‐Catalyzed Cascade Cyclization: Direct Synthesis of 3‐Substituted Phthalides from Aldehydes and Aromatic Acids

A novel rhodium(III)‐catalyzed direct functionalization of ortho C H bonds of benzoic acid derivatives and an intramolecular cyclization sequence generates 3‐substituted phthalides in moderate to good yields. This cascade cyclization involves a Grignard‐type arylation of an aldehyde and subsequent intramolecular nucleophilic substitution. No theoretical waste except for water is generated in the reaction.     

Evolution of the crystalline structure and cyclization with changing tension during the stabilization of polyacrylonitrile fibers

The effects of tension on the crystalline structure and cyclization of polyacrylonitrile fibers during stabilization were investigated. The degree of cyclization was measured by Fourier transform infrared spectroscopy and differential scanning calorimetry. The crystalline structure was characterized by wide‐angle X‐ray diffraction. When the fibers were heat‐treated at temperatures between 175 and 218°C, the tension mainly affected the cyclization in the amorphous regions through changes in the spatial distance of the chain segments; this led to a relatively higher cyclization degree under moderate tension. When the temperatures ranged from 226 to 232°C, the reactions extended to the crystalline regions. The chemical bonds became greater in the cross section of the fibers, and this was caused by cyclization structures formed in the former stage. Therefore, the optimum tension was higher than in the prior temperature range. At higher temperatures ranging from 238 to 270°C, a crosslinked structure formed, so the optimum tension increased continually. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42182.     

Titanium‐Catalyzed Enantioselective Synthesis of α‐Ambrinol

We describe the first enantioselective synthesis of the odorant compound (−)‐α‐ambrinol (96% ee) from commercial geranylacetone. The key steps are a Jacobsen’s asymmetric epoxidation and a titanium‐catalyzed stereoselective cyclization initiated by radical epoxide opening. The oxirane ring opening proceeds with retention of configuration at the epoxide chiral center, giving a secondary alcohol which can be advantageously exploited to raise the ee provided by the synthetic sequence. We also synthesized (+)‐α‐ambrinol by a closely related procedure, showing the synthetic versatility of combining titanium‐catalyzed cyclization with Jacobsen’s epoxidation reactions.     

Correlation of chemical shrinkage of polyacrylonitrile fibres with kinetics of cyclization

It has been established that the most important step in the production of carbon fibres from polyacrylonitrile (PAN) precursor fibres is the oxidative thermal treatment applied. During this treatment, physical phenomena and chemical reactions take place accompanied by the shrinkage of the fibres, which has a physical or chemical origin, depending on the nitrile cyclization reactions. The aim of the present study is to establish a correlation between the chemical shrinkage of PAN fibres and the kinetics of cyclization reactions. Based on the isothermal treatment of PAN fibres, we developed a method in order to distinguish between physical and chemical shrinkages. The onset time for the chemical shrinkage follows a relationship with temperature. Chemical shrinkage versus cyclization time data were fitted with the exponential rise to the maximum of the curves. Furthermore, the cyclization kinetics was studied using differential scanning calorimetry and the kinetic parameters determined were identical to those calculated from the chemical shrinkage, demonstrating that the latter is directly related to the kinetics of the cyclization reactions. It was therefore concluded that according to the method developed to distinguish the physical from the chemical shrinkages: (1) there exists a certain onset time for a given treatment temperature to trigger the chemical shrinkage; (2) cyclization reactions do not start below a limiting temperature of 168 °C; (3) at 340 °C, the temperature where the cyclization reactions are completed, the maximum shrinkage is 24%; and (4) the oxidized PAN fibres contain mainly ladder polymer structures with approximately symmetrical sequences connected in angled positions. Copyright © 2007 Society of Chemical Industry     

Effect of intramolecular cycles on the polycyclotrimerization of aromatic dicyanates

The gel conversions (α_gel) for the polycyclotrimerization of aromatic dicyanates are significantly higher than the classical mean-field value of 0.5. The reasons for the higher gel conversion, which is consistent with all experimental results of different structures of monomers, were inductively attributed to the accessibility effect of the functional group and the substitution effect, as well as the effect of the intramolecular cyclization. Nevertheless, the former two effects on the gel conversion can be quantitatively represented in terms of the extent of the intramolecular cyclization. Some theoretical expressions (including gel conversion and crosslink density with respect to the conversion) were derived by use of the recursive method with due consideration of the intramolecular cyclization. These expressions (with only one experimental parameter, α_gel) were found to be effective in describing gel fraction–conversion data for various polycyanurates. A dramatic change in the product value of ΔC_p · T_g was also found in the vicinity of the gel point for all different structures of aromatic dicyanate systems. The dramatic change in ΔC_p · T_g occurs at the gel point rather than the expected mean-field gel conversion of 0.5, presumably due to the intramolecular cyclization. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 1927–1938, 1999     

Structure evolution mechanism of polyacrylonitrile films incorporated with graphene oxide during oxidative stabilization

Oxidative stabilization is a key process for polyacrylonitrile (PAN)-based carbon materials. During this process, oxygen has a significant influence on the formation of cyclization structure and crosslinking structure of PAN matrix. Here, graphene oxide (GO) was used as filler in PAN matrix, the structure evolution of GO/PAN composite was studied during oxidative stabilization. Solubility measurement revealed that the crosslinking degree increased, while the cyclization degree of stabilized films decreased after GO incorporation. The effect of GO on the structure of PAN film was characterized by XRD, DSC, DMA, FTIR, and XPS. These results verified that GO could initiate the cyclization reaction of PAN at a lower temperature. The carboxylic groups on GO sheets might take part in the cyclization reactions during the heat treatment. Moreover, the oxygen-containing molecules released from GO decomposition during the heat treatment were beneficial to the formation of crosslinking structure. The possible mechanism of the structure evaluation was proposed in this article. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47701.     

Effect of electron beam irradiation on polyacrylonitrile precursor fibers and stabilization process

The electron beam was imposed on the polyacrylonitrile precursor fibers before the fibers were stabilized. The effect of electron beam irradiation on the chemical structure, transverse section, and surface morphology and thermal properties of the fibers in the process of stabilization was characterized by the use of Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and differential scanning calorimeter, respectively. A parameter η = I(C?N)/[I(C?N) + I(C?N)] was defined to evaluate the extent of cyclization in the stabilization process. The kinetic parameters, viz. activation energy (E) and pre‐exponential factor (A) of the stabilization reactions, were calculated by Kissinger method. FTIR analysis indicated that the cyclization of nitrile groups was initiated at room temperature by electron beam irradiation. The transformation of C?N groups to C?N ones was accelerated in the process of stabilization. The extent of cyclization of the stabilized fibers was increased. SEM analysis indicated that irradiation could also decrease the internal and surface defects of the stabilized fibers treated at 300°C. The activation energy of cyclization reaction was reduced from 302 to 280 kJ/mol and 260 kJ/mol through 100 and 200 kGy electron beam irradiation, respectively. The reaction temperature range was expanded, and the exothermic rate was slowed down in the process of stabilization, which was the reason why the stabilized fibers have improved cyclization degree and less internal defects. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Iron(III) Chloride and Diorganyl Diselenide‐Promoted Nucleophilic Closures of 1‐Benzyl‐2‐alkynylbenzenes in the Preparation of 9‐(Organoselanyl)‐5H‐benzo[7]annulenes

Iron‐promoted cyclization of 1‐benzyl‐2‐alkynylbenzenes with diorganyl diselenides led to the synthesis of 9‐(organoselanyl)‐5H‐benzo[7]annulenes whereby the mutual action between diorganyl diselenides and iron(III) chloride in a 0.5:1.0 mol ratio was essential in order to achieve the maximal yields of the products. The cyclization reaction tolerated a variety of functional groups, such as trifluoromethyl, chloro, fluoro and methoxy, in both the 1‐benzyl‐2‐alkynylbenzenes and the diorganyl diselenides, giving the seven‐membered heterocyclic products exclusively via a 7‐endo‐dig cyclization process.

     

Facile de Novo Sequencing of Tetrazine-Cyclized Peptides through UV-Induced Ring-Opening and Cleavage from the Solid Phase

While most FDA-approved peptide drugs are cyclic, the robust cyclization chemistry of peptides and the deconvolution of cyclic peptide sequences by using tandem mass spectrometry render cyclic peptide drug discovery difficult. Here we present the successful design of cyclic peptides on solid phase that addresses both of these problems. We demonstrate that this peptide cyclization method using dichloro-s-tetrazine on solid phase allows successful cyclization of a panel of random peptide sequences with various charges and hydrophobicities. The cyclic peptides can be linearized and cleaved from the solid phase by simple UV light irradiation, and we demonstrate that accurate sequence information can be obtained for the UV-cleaved linearized peptides by using tandem mass spectrometry. The tetrazine linker used in the cyclic peptides can further be explored for inverse electron-demand Diels-Alder (IEDDA) reactions for screening or bioconjugation applications in the future.     

Copper‐Mediated Oxidative Radical Addition/Cyclization Cascade: Synthesis of Trifluoromethylated and Sulfonated Quinoline‐2,4(1H,3H)‐diones

A copper‐mediated oxidative radical addition/cyclization cascade of o‐cyanoarylacrylamides with sodium trifluoromethanesulfonate (Langlois’ reagent) has been achieved. The reaction proceeds through radical addition, cyclization, and imine hydrolysis, in which the cyclization was accomplished by an intramolecular addition of the carbon radical to the nitrile. This transformation exhibits a wide substrate scope and good functional group tolerance, thus providing a highly efficient and practical access to a variety of trifluoromethylated quinoline‐2,4(1H,3H)‐diones. Furthermore, using other sulfinic acid sodium salts as sulfonylating agents, sulfonated quinolinediones were also obtained through a similar radical cascade.

     

Stereoselective Synthesis and Binding Properties of Novel Concave‐Shaped Indolizino[3,4‐b]quinolines

Novel all‐cis‐configurated indolizino[3,4‐b]quinoline receptors 3, 4 were prepared via diastereoselective Lewis acid‐catalyzed cyclization of N‐arylimines 6, 7 as the key step. In order to obtain the indolizino[3,4‐b]quinoline derivative 21 without a gem‐dimethyl group at C‐7, an N‐arylimine precursor 18 bearing a vinyldisilane terminus was prepared in 8 steps from L‐prolinol 15 . In contrast to the known β‐effect of silyl groups cyclization of 18 proceeded via an α‐carbenium ion species to give the diastereomeric products 19, 20, which were desilylated to 21, 22 . The association constants for receptors 2 — 4 and 21 decreased in the order 21 > 2 > 4 > 3 for both acetic acid and N‐Z‐phenylalanine as substrates.